This invention relates to light stabilized antimicrobial materials and methods of preparing antimicrobial polymers for use in wound dressings and medical devices.
Infection is a problem associated with wounds. Infection can retard wound healing, is traumatic for the patient and can significantly increase treatment costs and time. Consequently there is a need to both prevent and treat infection resulting from wounds or wounds in conjunction with of wound dressings, or the use of other medical devices. Examples of such devices at increased risk include prosthetic devices, implants, or wound dressings used on acute or chronic exudating wounds. This can be achieved by the use of topical antimicrobial agents.
It is known to include antimicrobial agents in materials used in the manufacture of medical devices such as wound dressings, ostomy appliances and others. One such antimicrobial agent is silver which is used in various forms such as salts or other silver compounds and which can be used in the fibers, polymers, textiles and adhesive components used in the fabrication of such devices. A problem with silver-containing materials is that they are typically sensitive to light which causes uncontrolled discoloration of the silver-containing material. Numerous efforts have been made to render such materials photostable, however there is still a need to enhance the photostabilization of silver in certain materials comprising hydrophilic, amphoteric and anionic polymers. This is especially true where such polymers are used in medical devices. Accordingly, improved light stabilized silver-containing polymers and methods for their manufacture have been sought.
U.S. Pat. No. 5,770,255 describes methods of forming anti-microbial coatings on the surface of medical devices. The coatings described include metal ions such as silver. However, this process requires higher than ambient gas pressures and low temperatures, which are inconvenient and costly. Further this process results in a distinct disadvantage that the coating alters the dimension of the medical device. Such changes in sizes of medical devices such as implants can affect the usefulness of the product. In addition, metal ions present as coatings on the surface of medical devices such as dressings may render the product toxic.
U.S. Pat. No. 5,326,567 describes methods of making silver-containing compositions for use in medical applications. The compositions contain acrylic polyether polymers such as polyethylene glycol and are coupled with silver nitrate. However, this system is only suitable for use in solutions and is very sensitive to solvent and salt conditions. Further, this system is unlikely to be sufficiently robust to survive sterilization, which is essential for wound dressings. Additionally, this system is unsuccessful when applied to fibrous or hydrocolloid wound dressings.
U.S. Pat. No. 3,422,183 discloses the use of ultraviolet irradiated silver fluoride compositions in items such as bandages. The ultraviolet treatment reportedly enhances the activity of the silver, but the problem of photostability is not resolved. Further, this process is problematic with respect to the safety of fluoride compounds in contact with wounds, particularly using concentrations of fluoride compounds that would be required to achieve efficacy.
U.S. Pat. No. 4,646,730 discloses light stable polyvinylpyrrolidene/silver sulfadiazine (PVP/SSD) hydrogel dressings, where the gel is formed by utilizing electron beam irradiation to crosslink the PVP. Photostabilization is reportedly provided adding magnesium trisilicate to the gel, and preferably by also adding hydrogen peroxide and/or polyacrylic acid. This process requires specialized equipment to carry out the beam irradiation. Further, this process uses a hydrogel and therefore would be incompatible with other wound dressing types and technologies.
WO 00/01973 describes stabilized antimicrobial compositions containing silver for use in wound dressings. The silver is in the form of a complex with a primary, secondary or tertiary amino and the complex is associated to one or more hydrophilic polymers. However, the method of processing limits the type of products that can be produced and also alters the release rate of silver. This process is better adapted to hydrocolloid products which, due to the adhesive matrix, suffers from low availability of silver. This system is unsuitable for application to water swellable/soluble materials once they have been formulated.
U.S. Pat. Nos. 4,906,466 and 5,413,788 disclose antimicrobial compositions suitable for topical use or wound care and which exhibit suppression of light instability. The compositions comprise an antimicrobial silver compound deposited on a physiologically inert oxidic synthetic support material in particulate form, such as titanium oxide. However, the resultant product has been found be susceptible to darkening due to the reduction of the silver compound to metallic silver. Further, the use of insoluble particulates such as titanium oxide as a support is not desirable in wound healing products because the particulates are considered to be foreign bodies and must be removed.
U.S. Pat. No. 4,446,124 relates to the use of ammoniated SSD incorporated into animal tissue to prepare burn dressings. The SSD is incorporated into the tissue by soaking the tissue in an ammoniacal SSD solution or suspension. While the ammonium solution is reported to increase the concentration of silver which can be incorporated into the dressing, photostabilization is not mentioned and is unlikely. Further, this process uses animal tissue as the substrate, which is undesirable for use in wounds.
In accordance with the present invention, a novel method for the preparation of light stabilized silver-containing hydrophilic, amphoteric and anionic polymers is disclosed. This invention describes simple and inexpensive methods for the preparation of such polymers that provide effective and non toxic antimicrobial activity in a water swellable material that can be terminally sterilized.
The present invention is directed to methods of preparing a material which contains one or more hydrophilic, amphoteric or anionic polymers, where the material has antimicrobial activity. Preferably, the material containing the polymer(s) is used in a medical device, a wound dressing, or an ostomy device. Also included in the present invention are polymers and materials prepared by the methods described herein. The present invention is advantageous over the prior art because it is easily applicable to water soluble and/or water swellable materials.
In the inventive method, a solution is prepared comprising an organic solvent and a source of silver. Typically, the source of silver is initially dissolved in water, and a solution is formed by mixing water with the organic solvent. The quantity of silver should be sufficient to provide a desired silver concentration in the material. Appropriate sources of silver include silver salts, such as silver nitrate, silver chloride, silver sulphates, silver lactate, silver bromide, silver acetate silver carbonate, silver iodide, silver citrate, silver laurate, silver deoxycholate, silver salicylate, silver paraaminobenzoate, silver paraaminosalicylate, and/or mixtures thereof Other appropriate sources of silver include but are not limited to any simple water and/or alcohol soluble silver salt.
Next, the polymer is subjected to the solution for a time that is sufficient to incorporate the desired silver concentration. During or after the period wherein the polymer is subjected to the solution, the polymer is subjected to one or more agents which facilitate the binding of the silver and the polymer together. Suitable agents include ammonia, ammonium salts, thiosulphates, chlorides, and/or peroxides. In one preferred embodiment, the agent is aqueous ammonium chloride.
The resultant material is substantially photostable upon drying of the material. However, the material will dissociate to release the silver if the material is rehydrated.